Journal
HUMAN IMMUNOLOGY
Volume 77, Issue 12, Pages 1147-1153Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.humimm.2016.08.004
Keywords
HLA-C; KIR; Natural killer cells; HIV-1
Categories
Funding
- PhenoGenetic Project at Brigham & Women's Hospital [RC2 GM093080]
- Ragon Institute
- National Institute of Health [R01 AI080289]
- NIH Harvard Center for AIDS Research [P30 AI060354-02]
- Frederick National Laboratory for Cancer Research [HHSN261200800001E]
- NIH, Frederick National Lab, Center for Cancer Research
Ask authors/readers for more resources
Differences in HLA-C expression are inversely correlated with HIV viral load set-point and slower progression to AIDS, linked to enhanced cytotoxic T cell immunity. Yet, beyond T cells, HLA-C serves as a dominant ligand for natural killer (NK) cell killer immunoglobulin-like receptors (KIR). Thus, we speculated that HLA-C expression levels may also impact NK activity, thereby modulating HIV antiviral control. Phenotypic and functional profiling was performed on freshly isolated PBMCs. HLA-C expression was linked to changes in NK subset distribution and licensing, particularly in HLA-C1/C1, KIR2DL3+2DL2-individuals. Moreover, high levels of HLA-C, were associated with reduced frequencies of anergic CD56(neg) NKs and lower frequencies of KIR2DL1/2/3+ NK cells, pointing to an HLA-C induced influence on the NK cell development in the absence of disease. In HIV infection, several spontaneous controllers, that expressed higher levels of HLA-C demonstrated robust NK-IFN-gamma secretion in response to target cells, highlighting a second disease induced licensing phenotype. Thus this population study points to a potential role for HLA-C levels both in NI(cell education and development. (C) 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available